Trial Outcomes & Findings for Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab (NCT NCT00238238)

NCT ID: NCT00238238

Last Updated: 2017-03-15

Results Overview

Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a \>/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 97 participants
• Primary outcome timeframe: Duration of treatment (12 cycles)
• Results posted on: 2017-03-15

Participant Flow

Between October 2006 and April 2011, 97 participants were accrued to the study.

Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Participant milestones

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Overall Study STARTED	3	48	46
Overall Study COMPLETED	3	45	46
Overall Study NOT COMPLETED	0	3	0

Reasons for withdrawal

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Overall Study Withdrawal by Subject	0	3	0

Baseline Characteristics

Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab

Baseline characteristics by cohort

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide n=45 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab n=46 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.	Total n=91 Participants Total of all reporting groups
Age, Continuous	—	63 years n=7 Participants	64 years n=5 Participants	63 years n=4 Participants
Sex: Female, Male Female	—	18 Participants n=7 Participants	19 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	—	27 Participants n=7 Participants	27 Participants n=5 Participants	54 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	—	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	—	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	—	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	—	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	—	37 Participants n=7 Participants	44 Participants n=5 Participants	81 Participants n=4 Participants
Race (NIH/OMB) More than one race	—	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	—	4 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	—	45 participants n=7 Participants	46 participants n=5 Participants	91 participants n=4 Participants

PRIMARY outcome

Timeframe: Duration of treatment (12 cycles)

Population: Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.

Outcome measures

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide n=45 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab n=46 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Overall Response Rate	—	53.3 percentage of participants Interval 37.9 to 68.3	76.1 percentage of participants Interval 61.2 to 87.4

PRIMARY outcome

Timeframe: Up to 10 years

Population: Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.

Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method.

Outcome measures

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide n=45 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab n=46 Participants Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Time to Progression	—	1.1 years Interval 0.8 to 1.2	2 years Interval 1.7 to 3.0

Adverse Events

Arm I - Rituximab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm II - Lenalidomide

Serious events: 8 serious events

Other events: 44 other events

Deaths: 0 deaths

Arm III - Lenalidomide and Rituximab

Serious events: 12 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide n=45 participants at risk Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab n=45 participants at risk Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Blood and lymphatic system disorders Febrile neutropenia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Blood and lymphatic system disorders Hemoglobin decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Sinus arrhythmia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Sinus tachycardia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Endocrine disorders Hypothyroidism	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Dry eye syndrome	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Vision blurred	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Abdominal distension	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Colitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Constipation	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Dysphagia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Ear, nose and throat examination abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Esophageal pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Hemorrhoids	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Nausea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Obstruction gastric	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Oral pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Vomiting	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Chest pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Chills	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Death NOS	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Disease progression	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Edema limbs	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Fatigue	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Fever	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Gait abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Immune system disorders Cytokine release syndrome	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Bronchitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Opportunistic infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Pneumonia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Sepsis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Skin infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Vaginal infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Injury, poisoning and procedural complications Intraoperative musculoskeletal injury	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Alanine aminotransferase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Alkaline phosphatase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Blood bilirubin increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Creatinine increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Electrocardiogram QTc interval prolonged	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations INR increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Leukocyte count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Lymphocyte count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Neutrophil count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Platelet count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Weight loss	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Alkalosis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Blood glucose increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Dehydration	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum albumin decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum calcium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum glucose decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum magnesium increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum phosphate decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum potassium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Neck pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor flare	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Dysgeusia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Ischemia cerebrovascular	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Mini mental status examination abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Neuralgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Seizure	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Speech disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Depression	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Insomnia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Kidney pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Proteinuria	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Renal failure	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Ureteric obstruction	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchospasm	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Dry skin	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Erythema multiforme	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Pruritus	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Sweating	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Flushing	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Hot flashes	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Hypotension	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Thrombosis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.

Other adverse events

Measure	Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22.	Arm II - Lenalidomide n=45 participants at risk Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days.	Arm III - Lenalidomide and Rituximab n=45 participants at risk Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29.
Blood and lymphatic system disorders Febrile neutropenia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Blood and lymphatic system disorders Hemoglobin decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	42.2% 19/45 • Number of events 89 90 participants, on Arms II and III, were evaluable for adverse events.	37.8% 17/45 • Number of events 86 90 participants, on Arms II and III, were evaluable for adverse events.
Blood and lymphatic system disorders Lymph node pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Cardiac disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Cardiac pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Left ventricular dysfunction	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Sinus bradycardia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Cardiac disorders Ventricular arrhythmia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Ear and labyrinth disorders Ear pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Ear and labyrinth disorders External ear pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Ear and labyrinth disorders Hearing impaired	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Endocrine disorders Hypothyroidism	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 24 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Dry eye syndrome	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Eye disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Glaucoma	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Eye disorders Watering eyes	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Abdominal distension	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Abdominal pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 9 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Anal hemorrhage	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Constipation	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	46.7% 21/45 • Number of events 40 90 participants, on Arms II and III, were evaluable for adverse events.	35.6% 16/45 • Number of events 45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	31.1% 14/45 • Number of events 46 90 participants, on Arms II and III, were evaluable for adverse events.	31.1% 14/45 • Number of events 34 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Dry mouth	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Dyspepsia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Ear, nose and throat examination abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Esophageal pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Esophagitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Gastrointestinal disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Gastroscopy abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Hemorrhoids	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Nausea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	35.6% 16/45 • Number of events 40 90 participants, on Arms II and III, were evaluable for adverse events.	26.7% 12/45 • Number of events 32 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Oral pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Rectal hemorrhage	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Stomach pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Toothache	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Gastrointestinal disorders Vomiting	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 9 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Chest pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Chills	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Edema limbs	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	20.0% 9/45 • Number of events 28 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Fatigue	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	77.8% 35/45 • Number of events 138 90 participants, on Arms II and III, were evaluable for adverse events.	73.3% 33/45 • Number of events 166 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Fever	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Flu-like symptoms	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders General symptom	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Localized edema	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
General disorders Pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.
Hepatobiliary disorders Gallbladder pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Immune system disorders Cytokine release syndrome	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	26.7% 12/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.
Immune system disorders Hypersensitivity	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Immune system disorders Immune system disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Bronchitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Catheter related infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Gastric infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Gingival infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Otitis media	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Pharyngitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Rhinitis infective	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Sinusitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Skin infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Tooth infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Tracheitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Upper respiratory infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Urinary tract infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.
Infections and infestations Vaginal infection	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Injury, poisoning and procedural complications Bruising	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Injury, poisoning and procedural complications Thermal burn	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Injury, poisoning and procedural complications Vascular access complication	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Alanine aminotransferase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 27 90 participants, on Arms II and III, were evaluable for adverse events.	20.0% 9/45 • Number of events 35 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Alkaline phosphatase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 14 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Aspartate aminotransferase increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 21 90 participants, on Arms II and III, were evaluable for adverse events.	22.2% 10/45 • Number of events 33 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Blood bilirubin increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 31 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Creatinine increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 10 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 14 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations INR increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Laboratory test abnormal	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Leukocyte count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	46.7% 21/45 • Number of events 86 90 participants, on Arms II and III, were evaluable for adverse events.	35.6% 16/45 • Number of events 131 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Lymphocyte count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	20.0% 9/45 • Number of events 21 90 participants, on Arms II and III, were evaluable for adverse events.	28.9% 13/45 • Number of events 80 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Neutrophil count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	42.2% 19/45 • Number of events 94 90 participants, on Arms II and III, were evaluable for adverse events.	55.6% 25/45 • Number of events 123 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Platelet count decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	55.6% 25/45 • Number of events 96 90 participants, on Arms II and III, were evaluable for adverse events.	51.1% 23/45 • Number of events 114 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Serum cholesterol increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Weight gain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Investigations Weight loss	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Anorexia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Blood glucose increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	33.3% 15/45 • Number of events 50 90 participants, on Arms II and III, were evaluable for adverse events.	31.1% 14/45 • Number of events 55 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Blood uric acid increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Glucose intolerance	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum albumin decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 18 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum calcium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 24 90 participants, on Arms II and III, were evaluable for adverse events.	22.2% 10/45 • Number of events 38 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum calcium increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum glucose decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 14 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum magnesium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum phosphate decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 10 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 23 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum potassium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 13 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 27 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum potassium increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 20 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum sodium increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Metabolism and nutrition disorders Serum triglycerides increased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 13 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Arthritis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Back pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 9 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 14 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Bone pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 20 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Myositis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Neck pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 9 90 participants, on Arms II and III, were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor flare	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Ataxia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Depressed level of consciousness	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Dizziness	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.	22.2% 10/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Dysgeusia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 18 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Headache	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.	11.1% 5/45 • Number of events 10 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Memory impairment	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Neuralgia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Neurological disorder NOS	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Olfactory nerve disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Peripheral motor neuropathy	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Peripheral sensory neuropathy	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	33.3% 15/45 • Number of events 32 90 participants, on Arms II and III, were evaluable for adverse events.	37.8% 17/45 • Number of events 51 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Syncope	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Tremor	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Nervous system disorders Trigeminal nerve disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Anxiety	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Depression	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Insomnia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 10 90 participants, on Arms II and III, were evaluable for adverse events.
Psychiatric disorders Libido decreased	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Bladder spasm	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Proteinuria	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Urinary frequency	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Urinary incontinence	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Renal and urinary disorders Urinary retention	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
Reproductive system and breast disorders Pelvic pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	20.0% 9/45 • Number of events 20 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Bronchospasm	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.	24.4% 11/45 • Number of events 30 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 13 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 14 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Nasal congestion	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 6 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Alopecia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 3 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Dry skin	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	15.6% 7/45 • Number of events 12 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Erythema multiforme	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	22.2% 10/45 • Number of events 15 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 22 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Petechiae	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	4.4% 2/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Pruritus	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	20.0% 9/45 • Number of events 17 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash desquamating	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	24.4% 11/45 • Number of events 16 90 participants, on Arms II and III, were evaluable for adverse events.	22.2% 10/45 • Number of events 13 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin disorder	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 9 90 participants, on Arms II and III, were evaluable for adverse events.	17.8% 8/45 • Number of events 11 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin hypopigmentation	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Skin ulceration	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Skin and subcutaneous tissue disorders Sweating	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	13.3% 6/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 4 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Hot flashes	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 8 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Hypotension	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	6.7% 3/45 • Number of events 5 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Peripheral ischemia	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 2 90 participants, on Arms II and III, were evaluable for adverse events.	0.00% 0/45 90 participants, on Arms II and III, were evaluable for adverse events.
Vascular disorders Thrombosis	— 0/0 90 participants, on Arms II and III, were evaluable for adverse events.	8.9% 4/45 • Number of events 7 90 participants, on Arms II and III, were evaluable for adverse events.	2.2% 1/45 • Number of events 1 90 participants, on Arms II and III, were evaluable for adverse events.

Additional Information

John P Leonard, M.D.

Meyer Cancer Center, Weill Cornell Medical College

Email: jpleonar@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60